POEMS (POLYNEUROPATHY, ORGANOMEGALY, ENDOCRINOPATHY, M PROTEIN, SKIN LESIONS) SYNDROME
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Arq Neuropsiquiatr 2007;65(2-B):516-520
POEMS (Polyneuropathy, Organomegaly,
Endocrinopathy, M protein,
Skin lesions) syndrome
A South America’s report
Ana Claudia Celestino Leite1,2; Osvaldo J.M. Nascimento1,
Marco Antonio Lima3, Maria José Andrada-Serpa4
ABSTRACT - The POEMS syndrome, also known as Crow-Fukase syndrome, is an unusual systemic dis-
order described mainly in Asian individuals. It is characterized by the presence of (P)polyneuropathy,
(O)organomegaly, (E)endocrinopathy, (M) M-protein, and (S) skin changes. Several other associated con-
dictions such as sclerotic bone lesions, Castleman disease, low-grade fever, edema and hematologic disor-
ders are usually seen. We describe five Brazilian patients with this syndrome. Two patients presented Cas-
tleman disease, one patient presented osteosclerotic myeloma and in two patients no associated condi-
tions were found.
Key words: peripheral neuropathy, POEMS, monoclonal protein.
POEMS (polineuropatia, organomegalia, endocrinopatia, proteína M, alterações de pele): rela-
to sul-americano
RESUMO - A síndrome POEMS, também conhecida como síndrome de Crow-Fukase é uma desordem sis-
têmica rara descrita principalmente em asiáticos. Ela é caracterizada pela presença de (P) polineuropatia,
(O) organomegalia, (E) endocrinopatia, (M) proteína M e (S) alterações de pele. Diversas outras manifesta-
ções, tais como lesões osteoescleróticas, doença de Castleman, febre baixa, edema e distúrbios hematoló-
gicos são freqüentemente observados. Apresentamos cinco pacientes brasileiros com esta síndrome. Dois
pacientes apresentaram diagnóstico de doença de Castleman, um paciente com mieloma osteoesclerótico
e em dois pacientes, nenhuma condição associada foi encontrada.
PALAVRAS-CHAVE: neuropatia periférica, POEMS, proteína monoclonal.
POEMS syndrome (PS), also known as Crow-Fukase ed individuals from other ethnic backgrounds have
syndrome, is an unusual systemic disorder character- also been described5. There is a male/female ratio
ized by the presence of (P) polyneuropathy, (O) or- of 2:15,6.
ganomegaly, (E) endocrinopathy, (M) M-protein, and We report five Brazilian non-Asian descendant
(S) skin changes1. It was firstly described by Scheink- patients with PS and discuss the clinical aspects and
er in 19382, and the acronym POEMS was coined in therapeutic options for this syndrome.
1980 by Bardwick et al.1. Although the acronym PO-
EMS describes the five more important features of CASES
this syndrome, several other manifestations including Case 1 – A 33 year- old man was admitted with a histo-
ry of paresthesias and progressive weakness in lower limbs
sclerotic bone lesions, Castleman disease, low-grade
that resulted in inability to walk, edema and trophic ulcer-
fever, infiltrative orbitopathy, finger clubbing, hyper-
ations in both ankles. The general physical examination
hidrosis, pleural effusion, ascites, edema and hema- showed the presence of skin hyperpigmentation and gy-
tologic disorders can be seen3,4. It has been report- necomastia. The neurological exam showed a right ptosis,
ed mainly in Japanese individuals, although affect- distal weakness in the lower limbs, absent deep tendon re-
1
Postgraduate Program on Neurology / Neuroscience from The Fluminense Federal University; 2Instituto de Hematologia do Estado do
Rio de Janeiro (HEMORIO); 3National Institute of Cancer; 4Evandro Chagas Research Institute (IPEC/FIOCRUZ), Rio de Janeiro RJ, Brazil.
Received 21 September 2006, received in final form 16 January 2007. Accepted 14 March 2007.
Dr. Osvaldo J.M. Nascimento - Avenida Sernambetiba 2916 / 1125 - 22620-172 Rio de Janeiro RJ - Brasil. E-mail: osvaldo_nascimento@
hotmail.comArq Neuropsiquiatr 2007;65(2-B) 517
flexes, and distal lower limbs hypoestesia. Complete blood
cell count, erythrocyte sedimentation rate (ESR) and serum
glucose were in normal range. Serologies for HIV, Hepatitis
C virus (HCV), Hepatitis B virus (HBV) and VDRL were neg-
ative. Serum protein electrophoresis showed an increased
gamma spike. An endocrine evaluation disclosed no abnor-
malities. CT scan revealed a lytic lesion in the frontal bone
extending through the right orbit and frontal sinus. Elec-
trophysiological (EMG) studies showed a symmetrical demy-
elinating polyneuropathy. Bone biopsy was done at the site
of the lesion and the histopathological analysis was sugges-
tive of a multiple myeloma. The patient underwent a surgi-
cal resection of the bone lesion and, two years later, he had
markedly recovered from the neurological symptoms. Fig 1. Sural nerve biopsy from Patient 2 showing loss of large
and small myelinated fibers. Some fibers present a thin myelin
Case 2 – A 37 year-old man was admitted due to a 3-
sheet (arrows) Toluidin blue, 40X.
year history of progressive back pain, weakness and pares-
thesias in lower limbs. Two months before the admission,
he also developed hyperhidrosis, five-kilogram weight loss
and sexual impotence. The general examination showed
the presence of small hypercromic lesions in the feet and
legs and bilateral axillary and inguinal lymphadenopathy.
The neurological exam revealed a distal leg weakness as-
sociated with absent deep tendon reflexes bilaterally. No
sensory deficits were observed. Laboratory tests showed a
normal blood count, ESR, serum glucose and renal func-
tion. Urine analysis revealed protein traces, but no Bence
Jones’ protein was detected. Serologies for HIV, HBV and
HCV as well as VDRL were negative. Protein electrophore-
sis disclosed a monoclonal IgG spike. Rheumatologic tests
were negative. Radiographic bone survey showed multiple
lesions, with a mixed lytic and sclerotic pattern in the supe-
rior diafisis of the left humerus, in the sacrum and femurs.
No organomegaly was observed on an abdominal and pel- Fig 2. Photomicrograph of sural nerve longitudinal section
vis CT scan. The cerebrospinal fluid (CSF) presented 1 cell/ from Patient 4 showing some mononuclear cells surrounding
mm3 and 98 mg/dL protein. EMG was consistent with a sen- a small endoneurial vessel. H & E, 40X.
sorimotor polyneuropathy with mixed axonal and demye-
linating features. Biopsy of a left axillary lymphnode was
suggestive of Castleman’s disease. Sural nerve biopsy dem- blood count, electrolytes, liver and renal functions. ESR was
onstrated no signs of inflammation. Semithin transverse 115 mm at first hour. Anti nuclear antibodies and rheuma-
sections showed evidence of mild demyelination and signs toid factor were negative. The serum protein electropho-
of axonal degeneration (Fig 1). Fibers with fine myelin were resis appeared polyclonal and an immunoelectrophoresis
observed in some fascicles, as well as groups with axonal re- was not done. CSF analysis showed no white cells, increased
generation (Fig 1). The dissociated fiber study demonstrat- protein content (129 mg/dL) and normal glucose content.
ed numerous ovoids of myelin indicating axonal degener- Bone X-ray survey did not reveal abnormalities. CT scan
ation and rare fibers with short demyelinated segments. of the abdomen demonstrated hepatosplenomegaly. Biop-
These features were suggestive of an axonal neuropathy sy of the cervical ganglion showed hyperplasia consistent
with signs of secondary demyelination. The patient was with Castleman disease. Bone marrow biopsy was consid-
lost to follow up. ered normal except for an increased number of plasmo-
cytes (approximately 6%). EMG was consistent with a distal
Case 3 – A 51 year old man presented with a 7 month- symmetric axonal sensory and motor neuropathy. Melpha-
history of paresthesias in both upper and lower extremi- lan and prednisone were started and the patient was dis-
ties associated with a 30 kilogram weight loss, sexual impo- charged one month later with partial improvement. Two
tence and gynecomastia. The general examination showed months after, he was admitted again due to anasarca, re-
skin thickening at hands and cervical and inguinal lymph- nal dysfunction and the skin lesions were worse, with a
adenopathy. The neurological examination demonstrated scleroderma like appearance. He refused treatment and left
an arreflexic tetraparesia associated with amyotrophy in the hospital against medical advice. He was admitted again
the lower limbs and distal hypoestesia. No cranial nerve nine months later with a diagnosis of adrenal insufficiency
deficits were observed. Laboratory tests presented normal and died soon after from sepsis.518 Arq Neuropsiquiatr 2007;65(2-B)
Case 4 – A 41-year-old man was admitted with an 18- the endoneurium and vessels of the subperineurium (Fig 2).
month history of burning dysaesthesias in a “stocking “ A moderate fibrosis in the epineurium and loss of myelin-
distribution associated with progressive weakness of the ic fibers were noticed. No amyloid deposits were observed.
lower limbs. He also developed skin hyperpigmentation, Teased- fiber preparations showed an intense loss of my-
ten-kilogram weight loss and sexual impotence. The gen- elin in fibers of all sizes and axonal degeneration. Extensive
eral exam showed a diffuse adenomegaly, hepatospleno- endoneurial edema was present. These features were con-
megaly and leg edema. The neurologic exam showed a sistent with a chronic predominantly axonal inflammatory
distal symmetric tetraparesia associated with hypotonia, neuropathy. Unfortunately no follow up information was
absent deep tendon reflexes and distal lower limb hypoes- available since the patient move to another city.
tesia. Protein electrophoresis presented polyclonal pattern.
CSF analysis demonstrated a high protein content (240 mg/ Case 5 – A 31-year-old male presented with a tetrapare-
dL), with normal cell count and glucose content. Serolog- sia associated with a 15-kilogram weight loss, diffuse skin
ic tests for Toxoplasma gondii, HSV, CMV, HTLV-1 and HIV hyperpigmentation, hypertrichosis, and sexual impotence.
as well as VDRL were negative. Radiographic bone survey On general examination, there were gynecomastia, ana-
demonstrated a single osteosclerotic lesion in iliac bone sarca, cervical and axillary adenomegaly and testicular at-
on the left side. EMG showed a demyelinating sensorimo- rophy. The neurological examination showed a distal sym-
tor polyneuropathy. Sural nerve biopsy presented small fo- metric tetraparesia with absent deep tendon reflexes. CSF
ci of mononuclear cells (lymphocytes and plasmocytes) in analysis disclosed no abnormalities. Protein electrophore-
Table. Clinical characteristics of five cases.
Characteristic Case 1 Case 2 Case 3 Case 4 Case 5
Polyneuropathy
Peripheral neuropathy + + + + +
Papilledema – – + – –
Cerebrospinal fluid protein above 50 mg/dL ND + + + –
Organomegaly
Hepatomegaly – – + + –
Splenomegaly – – + + –
Lymphadenopathy – + + + +
Castleman disease – + + – +
Endocrinopathy
Gynecomastia + – + – +
Sexual impotence – + + + +
Hypoadrenalism – – + – –
M component
Monoclonal protein – + (IgG) – – + (IgG)
Policlonal protein – – + + –
Abnormal protein electrophoresis + – – – –
Skin changes
Hyperpigmentation + + + + +
Hypertrichosis – – – – +
Thickening – – + – –
Extravascular volume overload
Peripheral edema + – + + +
Ascites – – + – –
Pleural effusion – – – – –
Bone lesions
Sclerotic only – – – + –
Lytic only + – – – –
Mixed sclerotic and lytic – + – – –
Other features
Weight loss > 5 kilograms – + + + +
Thrombocytosis – – – + –
Polycythemia – + – – –
ESR > 30mm at 1st hour – – + – –
Hyperhydrosis – + – – –
+, present; –, Absent; ND, not done; >, more than.Arq Neuropsiquiatr 2007;65(2-B) 519
sis showed a monoclonal IgG spike, but there was no Bence POEMS syndrome and the IgM neuropathies is that,
Jones protein. Radiographic bone survey disclosed no le- in the first one, immunoglobulin deposits are hardly
sions. Electrodiagnostic study disclosed reduction of senso- ever seen2.
ry and motor action potentials with positive sharp waves
and fibrillations in distal muscles consistent with an axonal Organomegaly (hepatomegaly, splenomegaly
polyneuropathy. Adenomegaly was observed on abdominal and/or adenomegaly) is present in 50-78% of the
CT scan. Bone marrow biopsy disclosed no abnormalities. affected individuals in different series2,5,6. Liver and
Biopsy of a lymph node showed angiofollicular lymphoid spleen enlargement are usually associated with nor-
lesion and sural nerve biopsy demonstrated loos of myelin- mal histological findings. However Castleman’s dis-
ated fibers and axonal degeneration. A diagnosis of PO-
ease is frequently diagnosed in patients with POEMS
EMS was made and the patient was treated with Melpha-
and adenomegaly5. In our study, all but one patient
lan and prednisone. The patient gradually improved from
the weakness and the endocrine manifestations. had organomegaly and three were diagnosed with
The clinical findings in the five cases are summarized Castleman’s disease.
in Table. A monoclonal plasmaproliferative disorder was
All of the patients gave their informed consent prior to
present in two out of five patients (patients 2 and 5).
their inclusion in the study.
Two additional patients had a protein electrophoresis
with a polyclonal pattern (patients 3 and 4). Immu-
Discussion nofixation is more sensitive than the serum protein
All patients in this study were men and the mean electrophoresis to the detection of a monoclonal pro-
age at onset was 37.8 years (range 31-51 years). tein2. Unfortunately, the first method was not avail-
There is a male preponderance of POEMS syndrome able. This could explain the absence of a monoclonal
as reported in Asian series as well as other South- spike in three patients. All patients had evidence of
American cases. In a review of 102 Japanese cases, an endocrinopathy at time of diagnosis. Clinical evi-
the mean age at onset was 46 years6. dence of gonadal axis dysfunction was observed in
Evidence of a peripheral neuropathy was present all five cases, although this was not confirmed by
in all five patients at the time of the first evaluation. laboratorial data. This could be explained by either
Neuropathic symptoms are the presenting feature in an absolute hyperestrogenemia or a relative one in
most of the individuals and its considered as require- a setting of hypoandrogenism. One patient devel-
ment for the diagnosis of POEMS2. Distal symmetric oped adrenal insufficiency later in the course of the
sensory loss, absence of the deep tendon reflexes and disease. It is an uncommon feature, being reported
progressive ascending weakness usually overshadow- in 16% of the patients in the series of Dispenzieri
ing the sensory symptoms are frequently seen2. EMG et al.2. Interestingly, none of the individuals in our
findings include slowing of nerve conduction velocities study had evidence of thyroid dysfunction or diabe-
predominantly in the intermediate nerve segments. tes mellitus.
Conduction block are rare. Decreased compound Skin changes associated to PS are characterized
muscle action potentials are typically observed in the by thickening, hypertricosis, hyperpigmentation,
lower than the upper limbs as seen in our cases7. clubbing, skin angiomas, acrocyanosis, plethora and
Autonomic dysfunction such a bradycardia and white nails3. The most common cutaneous lesion is
sphincterial disorders and cranial nerve involvement hyperpigmentation2, which can be diffuse or local-
are rarely seen. Patient 5 developed a syncopal state ized and is unrelated to adrenal insufficiency5. It was
with palmoplantar sweating in absence of adrenal seen in all individuals at the time of first evaluation.
insuficiency, suggesting an autonomic component. Hypertrichosis and skin thickening were present in
CSF protein concentration was increased in three pa- one patient each (patients 5 and 3, respectively).
tients as previously described6. The classic pattern of the bone lesions in POEMS
A sural nerve biopsy was performed in three pa- is a sclerotic or mixed sclerotic and lytic. They can be
tients. Histological analysis evidenced of a chronic solitary or multiple. Exclusively lytic lesions are seen
inflammatory axonal neuropathy with demyelinat- just in a small proportion of the patients2. Accord-
ing findings. Both axonal and demyelinating lesions ing to Soubrier et al.5 prognosis is better for solitary
have been described in association with POEMS8. The bone lesions, but this was not confirmed in a recent
endoneurial edema, as seen in Case 4, points toward larger series2.
an alteration in the blood-nerve barrier considered Extravascular volume overload is a less recognized
by Koike and Sobue8. A major difference between aspect of the POEMS, although it is present in a great520 Arq Neuropsiquiatr 2007;65(2-B)
percentage of the affected individuals6. Four out of To summarize, we presented the largest series of
five patients in this series had peripheral edema or South American patients with POEMS and reviewed
ascites either at presentation or during the course of the clinical and laboratorial features of this disease.
disease. Its pathogenesis is not fully understood but This rare syndrome should be included in the differ-
there is evidence of a systemic disturbance of the ential diagnosis of acquired neuropathies associated
vascular permeability5. with multisystemic manifestations.
There are several other manifestations that have
been observed in association with POEMS. Hyperhi- References
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ick DL. Plasma cell dyscrasia with polyneuropathy, organomegaly, en-
ESR were present in one patient each (Table). Weight docrinopathy, M protein, and skin changes: the POEMS syndrome. Re-
loss greater than five kilograms was common being port on two cases and a review of the literature. Medicine (Baltimore)
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dependent of the number of the POEMS features2. drome, and a review of the literature. Blood 2004.You can also read
